Identification of Bacterial DNA in the Peripheral Blood of Patients With Active Psoriasis

Psoriasis is a systemic autoimmune inflammatory disease that shares some immunological aspects with other inflammatory-based diseases, such as Crohn disease.¹ Bacterial DNA (bactDNA) fragments have been shown to induce a systemic immunological response in Crohn disease and other settings.^2,3 Although the results of most blood bacterial cultures are negative in patients with psoriasis, we hypothesized that the presence of bactDNA in the blood might act as a molecular trigger in disease outbreaks and induce a systemic inflammatory response in these patients.

This study included a consecutive series of patients whose psoriasis had previously cleared or was being controlled exclusively with topical medications who had a new flare of psoriasis and a group of sex- and age-matched control participants without psoriasis. The study protocol was approved by the Research Ethics Committee of the Hospital General Universitario de Alicante and all patients gave written informed consent. Exclusion criteria were the use of systemic corticosteroids, methotrexate sodium, cyclosporine, or anti–tumor necrosis factor drugs in the previous 3 months, antibiotic use in the previous 2 weeks, and the concomitant diagnosis of cirrhosis, intestinal bowel disease, and signs of bacterial infection. At the time of inclusion, patients were classified into severe, severe to moderate, moderate, or slight psoriasis, according to the international Psoriasis Area Severity Index.

A peripheral blood sample was collected from all participants and analyzed for routine biochemical laboratory values as well as interleukin (IL) 1B, IL-6, IL-12, tumor necrosis factor, and interferon γ levels. An aliquot of blood was inoculated under aseptic conditions in sterile, rubber-sealed Vacutainer SST II tubes (BD Diagnostics) to detect and identify bactDNA in the blood, as described previously.⁴ Statistical analyses were performed using SPSS, version 22 (IBM). The odds ratio and 95% CIs were determined as a measure of effect size. P < .05 was considered significant.

Fifty-four patients with psoriasis and 27 controls were included in the study. The baseline characteristics of these participants are shown in Table 1. Blood bactDNA was present in 16 patients with psoriasis, all of whom showed the phenotype of plaque psoriasis (16 of 45 [35.5%]), whereas 6 patients with guttate psoriasis, 3 with inverse psoriasis, and all 27 controls did not have bactDNA in the blood. Species identification corresponded to Escherichia coli (n = 9), Klebsiella pneumoniae (n = 2), Enterococcus faecalis (n = 2), Proteus mirabilis (n = 1), Streptococus pyogenes (n = 1), and Shigella fresneli (n = 1).

A higher proportion of findings of bactDNA in the blood was observed in patients with plaque psoriasis compared with patients with other psoriasis phenotypes (35.5% vs 0%; P < .05). The patient’s age at diagnosis of psoriasis and years since the first episode of psoriasis showed statistically significant differences in patients with and without bactDNA in the blood. The systemic inflammatory response was significantly higher in patients with bactDNA compared with other patients and controls (Table 2).

In the patients with psoriasis in this study, bactDNA was associated with increased levels of IL-1β, IL-6, IL-12, tumor necrosis factor, and interferon γ. BactDNA induces a potent immune response by joining toll-like receptor 9 in immune cells.⁴ The levels of cytokines in patients with psoriasis and bactDNA in the blood were significantly higher than those of patients with psoriasis without evidence of bactDNA. Moreover, the presence of bactDNA was evident in patients with longer duration of the disease and in those whose disease was evident at a younger age (Table 2). It may be that the presence of bactDNA identifies a subset of patients with a more aggressive course of psoriasis.

Nucleotide sequencing revealed that E coli was the most prevalent source of bactDNA (9 of 16 isolates). The rest of the bacterial species’origin of the detected genomic fragments also corresponded to the type of flora commonly found in the intestinal lumen. Therefore, the bactDNA detected in our patients with psoriasis may have their origin in the intestinal lumen.⁵ Supporting this hypothesis is the fact that intestinal permeability has already been reported to be increased in patients with psoriasis.⁶ Taken together, these data suggest a role for bactDNA translocation in active plaque psoriasis.

Accepted for Publication: December 11, 2014.

Corresponding Author: Vicente Navarro-López, MD, Unidad de Investigación Clínica, Centro Dermatológico Estético de Alicante, Calle Alonso Cano, 51, 03014 Alicante, Spain (vnavarro@centrodermatologicoestetico.com).

Published Online: March 11, 2015. doi:10.1001/jamadermatol.2014.5585.

Author Contributions: Drs Navarro-López and Ramírez-Boscá had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Ramírez-Boscá, Navarro-López, Such.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Navarro-López, Such.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Navarro-López.

Administrative, technical, or material support: Martínez-Andrés, Francés, Asín-Llorca.

Study supervision: All authors.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Encarna Espejo-Luna, BSN, Centro Dermatologico Estetico de Alicante, Spain, provided clinical contributions and effort into this work. She was not financially compensated.